of hepatotoxicity [30–33], including CYP2E1 potentiation of LPS or TNF-α liver injury [34,35]. Activated JNK can phosphorylate and thereby inactivate Bcl-2 and Bcl-XL [62]. Levels of these two anti-apoptotic proteins were lowered by chronic ethanol feeding in CYP2E1 KI mice in association with activation of JNK, but not in the CYP2E1 KO mice in which JNK was not activated by the ethanol feeding. Despite this decline in levels of Bcl-2 and Bcl-XL, the ethanol injury was necrotic not apoptotic. While chronic ethanol-induced liver injury was usually considered to be necrotic [4,5,8], ethanol-induced apoptosis has also been observed [36,50]. Most likely whether liver injury induced by ethanol is necrotic or apoptotic or necroapoptotic may reflect amount of and time of ethanol feeding, mode of ethanol administration, whether significant endotoxemia occurs, the severity of mitochondrial injury and ATP depletion, the mouse strain and other factors such as pro and anti inflammatory cytokine elevation, fat content, type of fat. We have not yet assayed levels of proapoptotic members of the Bcl-2 family or ATP levels which may regulate a possible switch between apoptosis and necrosis in the CYP2E1 KI mice, nor conducted time courses of ethanol feeding to assess if an early apoptosis
